1 AMERICAN JOURNAL OF INDUSTRIAL MEDICINE (2009) Case Control Study of Pleural Mesothelioma in Workers With Social Security in Mexico Guadalupe Aguilar-Madrid, MD, MSc, PhD, 1 Eduardo Robles-Pérez, MD, MSc, 2 Cuauhtémoc Arturo Juárez-Pérez, MD, MSc, 1 Isabel Alvarado-Cabrero, MD, 3 Flavio Gerardo Rico-Méndez, MD, 4 and Kelly-García Javier, MD 3 Background Environmental and occupational exposure to asbestos in Mexico in the past has been a cause of deaths and health damages. Its magnitude is unknown to date. Our objective was to identify the proportion of cases of malignant pleural mesothelioma (MPM) that can be attributed to and occupational exposure to asbestos. Methods We carried out a case control study of MPM in 472 workers insured by the Mexican Institute of Social Security, all Valley of Mexico residents, with 119 incident cases and 353 controls. Cases were histologically confirmed. Participants were questioned concerning their occupational history and sociodemographic data. Assignment to one of the four exposures was performed qualitatively by an expert hygienist. Odds ratios (ORs) and attributable risks (ARs) were calculated using a non-conditional logistic regression model. Results A total of 80.6% of cases and 31.5% of controls had occupational exposure to asbestos. ORs were adjusted for age and gender and by exposure category, and exhibited an increase with probability of exposure as follows: 3.7(95% CI ) for the likely category and 14.3(95% CI 8 26) for the certain category; AR in the group occupationally exposed to asbestos was 83.2%, and the population AR was 44%. Conclusions Our results show that the relationship between industrial uses of all forms of asbestos is generating an increase in mesothelioma-related diseases and deaths among Mexican workers. As a public health policy, Mexico should prohibit the use of asbestos in all production processes with the aim of controlling the epidemic and preventing the occurrence of new cases of MPM. Am. J. Ind. Med ß 2009 Wiley-Liss, Inc. KEY WORDS: pleural mesothelioma; Insured workers; case controls; social security; Mexico INTRODUCTION Exposure to asbestos is well identified as an occupational risk, as is its carcinogeniceffect on lungs, pleura, and peritoneum [Selikoff et al., 1965; Mossman and Gee, 1989] Malignant pleural mesothelioma (MPM) in industrialized countries is caused predominantly by exposure to asbestos fibers [Selikoff, 1979; Rösler et al., 1994]. The International 1 Unidad de Investigacio n en Salud en el Trabajo, Instituto Mexicano del Seguro Social (Occupational Health ResearchUnit,Mexican Institute of Social Security - IMSS),Mexico City, Mexico 2 Coordinacio n de Salud en el Trabajo (Coordination of Occupational Health), IMSS,Mexico City, Mexico 3 Unidad Me dica de Alta Especialidad, Hospital de Oncologi a, Centro Me dico Nacional Siglo XXI (High Specialization Medical Unit, Oncology Hospital, Siglo XXI National Medical Center - CMN-SXXI) (Servicio detora x y Jefatura de Patologi a del IMSS^Thorax Clinic and Pathology Department, IMSS) Mexico City, Mexico 4 Hospital General Gaudencio Gonza lez Garza, Centro Me dico La Raza (Gaudencio Gonza lez Garza General Hospital, La Raza Medical Center), IMSS, Mexico City, Mexico Contractgrantsponsor:Irving J. SelikoffInternational Scholarof the Mount Sinai School of Medicine; Contract grant number: D43TW000640; Contract grant sponsor: Mount Sinai School of Medicine and Queens College, City University of NewYork; Contract grant sponsor: Fondo de Fomento a la Investigacio n (FOFOI); Contract grantnumber: ; Contract grant sponsor: Consejo Nacional de Ciencia ytecnologi a-me xico (CONACyT-Salud); Contract grant number: 2002-C *Correspondence to: Guadalupe Aguilar-Madrid, Unidad de Investigacio n en Salud en el Trabajo, Instituto Mexicano del Seguro Social, Centro Me dico Nacional Siglo XXI, Av. Cuauhte moc No. 330, Edif. C, 1er piso, Col. Doctores, Me xico, D.F., Mexico. Accepted 26 September 2009 DOI /ajim Published online in Wiley InterScience (www.interscience.wiley.com) ß2009Wiley-Liss,Inc.
2 2 Aguilar-Madrid et al. Agency for Research on Cancer [IARC, 1977] has considered asbestos a carcinogenic since 1977, as has the International Program on Chemical Safety  since Diverse studies have demonstrated the negative impact of exposure to the fiber on workers health [Selikoff et al., 1965; McDonald et al., 1984; Yano et al., 2001]. In Mexico, chrysotile or white asbestos is the type of fiber most frequently utilized in the industry and represents the most important exposure source for Mexican workers. Mexico has imported asbestos since 1932, but it was not until the 1970s that the most industries employing these fibers were installed in the country [Gavira et al., 1990; Aguilar- Madrid et al., 2003]. Ample international scientific evidence has emphatically demonstrated that all asbestos forms are carcinogenic, that they cause pleural mesothelioma, that there is no safe asbestos-exposure level, and the World Health Organization [WHO 2006] have requested its ban. Despite all this evidence, the proportion of MPM cases that can be attributed to environmental and occupational exposure remains unknown in Mexico; this has thus contributed to the lack of recognition of this exposure as an occupational risk. As a result, its medical care costs and pensions for workers and their families are absorbed by Social Security and the national health system. Despite the well-known health effects of asbestos exposure, there exists an international policy spearheaded by Canada to continue revitalizing the safe use of chrysotile, which implies a clear transfer of dangerous industries to less-industrialized countries such as Mexico, which possess a weak and inefficient judicial framework for worker protection. This will have damaging effects on health and an important impact in Mexico; similar to what has occurred since the 1970s in more industrialized countries, such as France, which has an incidence of 1,000 2,000 cases annually [Huré, 2006]. The aim of the present study was to determine the proportion of cases of MPM that are attributable to occupational exposure to asbestos in Mexican workers insured by the Mexican Institute of Social Security. METHODS We carried out a case control study of malignant pleural mesothelioma (MPM) incidence in Mexican insured workers at two concentration hospitals of this cancer type at different Instituto Mexicano del Seguro Social (Mexican Institute of Social Security IMSS) hospitals are located in the Valley of Mexico. One of these was La Raza General Hospital (Pulmonary and another the Oncology Hospital at the Siglo XII National Medical Center (Thorax Service); the latter is the referral center for four Mexican States including the Distrito Federal and the States of Mexico, Morelos, and Hidalgo, where all workers with MPM are referred to for medical care. The study period was from May 2004 to April 20, The research protocol was approved by the IMSS National Research Commission s Ethics Committee. Study participants signed informed consent and physicians from the participating hospitals were invited to collaborate in the study. The IMSS is the Mexican Institute of Social Security. It insures more than 12,000,000 workers, who represent 30% of the country s economically active population (45 million). The IMSS is divided into four regions of Mexico (North, West, Central, and South); each of these regions has a highly specialized Medical Center that includes an Oncology Hospital, which serves as the referral center for cancer cases. The hospitals participating in this study were from the Central region of Mexico, with 3,706,755 active insured workers and 71,681 retirees. The cases and controls in this study were selected from this population and the data were obtained from records of the Sistema Nacional de Derechohabientes [SINDO, National System of Policyholders] and the Sistema de Información de Trabajadores Pensionados de Cesantía, Edad Avanzada y Vejez IMSS [Information System of Retired Workers]. The cases were recruited from insured workers who were referred for medical care due to suspected diagnosis of MPM at any of the previously mentioned hospitals. Diagnosis of mesothelioma was confirmed by Oncologists and the Head of the Ward at the CMN-SXXI Oncology Hospital based on clinical review of the data (clinical history, X-ray films, computed tomography [CT] scans of the thorax and laboratory tests) and in the immunohistopathology study report. In the study, we only included cases in which MPM was confirmed by immunohistopathology study carried out by two pathologists who were certified by the Mexican Council of Pathology. The participation rate of cases was 99.1%; only one worker declined to participate, due to his extremely serious condition. Controls were selected at a proportion of three cases per control, with an age range of 5 years, with similar gender proportions, same insurance type (active workers and retirees), and same city of residence as well. These controls were randomly selected from the IMSS insured-worker population database and from the same Central region of the SINDO from which the cases originated. A database of 500 eligible workers was constructed: 250 were active workers and 250 were retired. The controls selected were referred to Unidades de Medicina Familiar (UMFs, Family Medicine Units), where they received medical care; by means of telephone calls and telegrams were sent to their homes and were invited to participate in the study. We included as controls insured workers who agreed to sign an informed consent letter and the questionnaire application. The
3 Case Control Study of Pleural Mesothelioma 3 participation rate was 59% for active workers and 83.2% for retired workers. Reasons for non-participation included the following: the person was not found at the address given; the individual worked in other States or outside of Mexico. For retired workers, non-participation was due to their living at other domiciles where someone was in charge of their care. Data Collection A standardized questionnaire was applied face to face to the workers by previously trained female interviewers whose background was social work; the questionnaire had been pilot tested in a healthy worker population. The instrument was designed to collect data on personal identification; socioeconomic aspects; worker employment history detailing initiation and termination dates for each of their jobs; type of industries; occupation in the company within the formal or informal economy; substances and raw materials utilized, intermediate and final products; a detailed description of their activities; and work site safety and hygiene conditions. Based on these data, insured workers were grouped according to the International Standard Industrial Code (ISIC) third review; for workplace, we used the 5-digit International Standard Classification of Occupations-88 (ISCO) of the International Labour Organization (ILO). In addition, we gathered data on para-occupational exposures, that is, the occupational history of the father or another family member, as well as information regarding likely environmental asbestos exposure, such as years of residence near asbestos industries. Furthermore, we requested information on smoking and calculated the smoking index as follows: number of cigarettes smoked daily multiplied by years of duration of the smoking habit divided by 20 (the number of cigarettes in a pack); this result was expressed in the number of cigarette packs smoked annually [Villalba and Martínez, 2004]. Assignment to Occupational Asbestos Exposure Category For this assignment, we utilized the ISIC revision 3.0, and occupational post, large-group headings, main subgroups, and primary groups from the ISCO-88. Qualitative Exposure Categories A database was constructed according to work history information and a detailed description of worker tasks. An industrial hygiene expert was blinded to the condition of each participant as case or control, thus ensuring that the data were coded blindly by workplace, economic activity, and time of initiation and termination of each employment. The hygienist had the work history data, as well as a list of the asbestos-importing industries in Mexico and those that manufactured asbestos in diverse forms (we possessed information on the 1887 companies located in Mexico that import asbestos) [Aguilar-Madrid et al., 2003]. The list was supplied by the Secretaría de Fomento Industrial (SECOFI, The Ministry of Industrial Promotion). Additionally, the hygienist had access to information from the international literature on different economic activities and workplaces known to involve asbestos exposure [Hammad et al., 1979; Thomas et al., 1982; Dement et al., 1983; Ohlson and Hogstedt, 1985; Peto et al., 1985; Gardner et al., 1986; Hughes et al., 1987; Ribak et al., 1989; Albin et al., 1990; Neuberger and Kundi, 1990; Chrostowski et al., 1991; Maltoni et al., 1994; Finkelstein, 1996; Burdorf and Swuste, 1999; Sali and Boffetta, 2000] that allowed us to estimate asbestos exposure in four categories, as follows: certain, when the worker mentioned direct or indirect occupational exposure to asbestos; likely, when the worker had been employed at companies known to have a high risk of asbestos, but the worker mentioned not being aware of it (for example: manufacturing asbestos cement products, manufacturing brake lining or clutch plates, transporting asbestos, insulation asbestos, worker in a power station) ; possible, when the worker was employed in industries known to have an asbestos exposure risk, but the worker did not report these as known and non-exposed (examples: working with furnaces, wearing heat protective clothing, construction site work, working in the plastic industry or rubber industry, working with sugar-cane). This classification is similar to that used by Rees in South Africa [Rees et al., 1999]. Statistical Analysis Exploratory data analysis was performed using STATA 9.0 SE statistical software package. We conducted a distribution analysis of continuous variables, analysis of variance between case and control groups, and calculated odds ratios (ORs) per group, as well as differences of proportions and of means between the groups. Based on nonconditional logistic regression model in which crude ORs were calculated and adjusted to take into account potential confounders and interactions. Also we performed analysis of residuals to determine goodness of fit and predictive value. Finally, based on the model, attributable risk (AR) was estimated in exposed workers and for the population at large based on formulas used by Szklo and Nieto  and Coughlin et al.  for regression models in case control studies. RESULTS The study comprised 472 workers, of whom 119 were incident cases and 353 healthy controls; 86.2% (407) were males and 13.8% (65) females. Their mean age was
4 4 Aguilar-Madrid et al years, with a standard deviation (SD) of 11.7 years, and a range of years; the mean age by gender was 61 years (SD 14.4 years) and 55.6 years (SD 12.5 years) in males and females, respectively, with a statistically significant difference. A total of 58% (69) cases and 58.9% (208) controls were retirees; the mean age was 46 years (SD 9 years) in active workers and 70 years (SD 6 years) in retirees. Cases were from the same populational source from which controls were selected; 63% (75) of cases and 51% (180) of controls were from the State of Mexico (Table I). A total of 8.4% (10) cases and 30% (106) controls were smokers at the time. The mean smoking index was 12.5 and 12.8 packs of cigarettes per year, respectively. With respect to education, 6% (7) cases and 2.5% (9) controls were illiterate; the proportions of elementary (primary) education were 45.7% (49) cases and 45.7% (149) controls, 54% did not finish their studies, indicating a low level of schooling in workers participating in the study. Of the exposure categories 69% (82) were in the certain category, as were 21.5% (76) of controls, with a statistically significant difference. Duration of exposure to asbestos >13 years was 61% (59) in cases and 38.7% in controls, with a statistically significant difference (Table I). A 50% of cases had a monthly income of 1.5 minimum wages, while controls earned 2.0 salaries per month, with a significant difference (Table II). The overall proportion of certain, likely, and possible occupational asbestos exposure in some workplaces with exposure of asbestos during the worker s entire work-life was 80.6% (96) in cases and 31.5% (111) controls, which was statistically significant (Table I). The occupational seniority means in asbestos exposurerelated workplace were significantly different between cases (20 years) and controls (14.6 years). The mean number of workplaces with asbestos exposure was two for both groups (Table II). The 119 cases of mesothelioma confirmed by histologic tests were analyzed by the Oncology Hospital s Chair of the Pathology Service at the CMN-XXI. A random sample of 33 cases was selected with their respective slides, and a second reading was performed by a Pathologist from the Instituto Nacional de Enfermedades Respiratorias (INER, National Institute of Respiratory Diseases) of the Secretaría de Salud de México (SSA, Mexican Ministry of Health). Agreement was determined for diagnosis of mesothelioma and mesothelioma type (malignant epithelial, sarcomatoid, malignant desiduoid). The Kappa test result was 82.2%, which according to Altam  and Byrt  is a very good agreement assessment, as referred by Szklo and Nieto . Table III shows the distribution of work periods of cases and controls according to work-life initiation date and exposure categories, in which the greatest proportion of the certain exposure category is observed after , the TABLE I. Frequency Differences Between Mesothelioma Cases and Controls in IMSS-Insured Workers (2004^2006) Case Control Variable N % N % Gender** Males Females Insurance type** Active workers Retired workers Marital status** Single Married Widowed Divorced Common law marriage Smoking Currently smoker Never smoked Smoker in the past Age categories (years)* 31^ ^ ^ Instruction** Illiterate Elementary Middle school Technical High school Undergraduate Master Place of residence** Distrito Federal State of Mexico Occupational exposure categories* No exposure Possible exposure Likely exposure Certain exposure Time of exposure* 13 years >13 years Instituto Mexicano del Seguro Social (Mexican Institute of Social Security). *Pearson w 2, < **Pearson w 2 >0.001.
5 Case Control Study of Pleural Mesothelioma 5 TABLE II. Comparison Between Cases and Controls IMSS-Insured Workers (2004^2006) Case Control Variable N Mean SD Range N Mean SD Range Age (years)** ^ ^85 Active workers ^ ^65 Retired ^ ^85 Monthly income in USD* ^1, ^2727 Smoking index (packs of cigarettes per year)** ^ ^102.6 Occupational seniority with exposure to asbestos (years)* ^ ^52 Possible ^ ^44 Likely ^ ^36.5 Certain ^ ^52 Number of workplaces with exposure to asbestos** ^ ^6 MPM, malignant pleural mesothelioma; SD, standard deviation. $10 Mexican pesos ¼ roughly $1US dollar (USD). *P < **P > period of greatest asbestos industry installation activity in Mexico [Gavira et al., 1990; Aguilar-Madrid et al., 2003]. There were a total of 42 work positions distributed among 27 economic activities that were considered to involve an asbestos exposure risk (Table IV). The greatest proportion of cases included individuals who worked in the manufacture of other non-metallic mineral products 15.6% (15), such as occupations involving the manufacture of products with asbestos (water tanks and asbestos-cement sheets, brakes, and clutches), mainly manufacturing industry laborers 12.5% (12), followed by construction industry workers such as bricklayers and building maintenance handymen, occupations that were well known for their high risk of exposure to asbestos (Table IV). Table V shows crude and adjusted ORs for certain, likely and possible strata that were calculated through a nonconditional logistic regression model, adjusted by gender and age as continuous variables. The adjusted ORs (aor) for each exposure category, with 95% confidence intervals were as follows: the certain exposure category had an aor ¼ 14.3 (95% CI 8 26), while the likely exposure category had an OR ¼ 3.7 (95% CI ), and the possible category an OR of 7.7 (95% CI ) The model clearly showed an increase in the risk of developing pleural mesothelioma with greater accuracy of asbestos-exposure data. Furthermore, we carried out the analysis of the residuals of the model, applying goodness-offit tests and testing the assumptions of the generalized linear models Based on non-conditional logistic regression model data, 76.27% of cases and controls were correctly classified; in addition, the model data allowed us to calculate the proportion of asbestos exposures among cases (52.9%) and controls (15.8%), and obtain the overall model OR ¼ 6 (95% TABLE III. Distribution of Job Periods AmongWorkers, According to Exposure Category and Decade of Initiation (Mexico, Case^Control Study, 2004^2006) Prior to ^ ^ ^ ^2006 Probabilityof exposure N % N % N % N % N % Cases Certain Likely Possible Total (96) Controls Certain Likely Possible Total (111)
6 6 Aguilar-Madrid et al. TABLE IV. Most Frequent Industrial Activities and Occupations by Initiation of Occupational Life Cases Controls N % N % Economic activity (two-digit ISIC. Revision 3.0) 26-Manufacture of other non-metallic mineral products Construction Sale, maintenance andrepairofmotor vehicles andmotorcycles; retail sale ofautomotivefuel Manufacture of basic metals Manufacture of fabricated metal products, except machinery and equipment Manufacture of furniture; manufacturing n.e.c Electricity, gas, steam and hot water supply Manufacture of food products and beverages Manufacture of rubber and plastics products Other industries Occupation (five-digit ISCO 88) Bricklayer, stonemason Carpenter Setter operator, soldering Mechanic, automobile Mechanic Industrial machinery Furnace-operator, converting/steel Collector, garbage Handyman building maintenance Laborer, manufacturing Other professions Total ISCO, International Standardized Classification of Occupations; ISIC International Standard Industrial Classification of All Economic Activities. CI, ). These data allowed us to calculate the attributable risk (AR) in exposed workers and for the population with the formula described by Szklo and Nieto  and Coughlin et al. , as follows: AR in exposed workers (ARE) ¼ OR 1/OR ¼ 6 1/6 ¼ ¼ 83.2%, TABLE V. Crude and Adjusted Odds Ratios in Cases and Controls of Malignant Pleural Mesothelioma in the Non-Conditional Logistic Regression Model Crude OR Adjusted OR (95% CI) a (95% CI) a Exposure categories Not exposed 1 1 Possible 6 (2.2^15.8) 7.7 (2.8^21.2) Likely 3 (1.1^8.1) 3.7 (1.3^10.4) Certain 11.3 (6.6^19.2) 14.3 (8^26) Gender 2.5 (1.1^5.6) Age 1.01 (0.99^1.02) OR, odds ratio; 95% CI, 95% confidence interval. a Age- and gender-adjusted in the non-conditional logistic regression model. with a 95% CI ( ). The population AR (ARP) was calculated as: (proportion of exposure in cases proportion of exposure in controls)/1 proportion of exposure in controls ¼ ( )/ ¼ ¼ 44%. DISCUSSION Comparison of our results with those of other international studies of MPM cases and controls and occupational asbestos exposure is not easy, due to different instruments, methods, and criteria for estimating and evaluating occupational exposure retrospectively. Nonetheless, results of case control MPM studies and asbestos exposure are very similar to ours, such as seeing in Table VI. Also, our findings show that the pattern of this relationship observed in the more industrialized countries during the 1970s is being repeated at present in Mexico. The results of the present study depend on the estimation of asbestos exposure by the expert hygienist, who could introduce bias as a result of nondifferential misclassification. The hygienist was blinded with regard to disease classification of the subject; thus the direction of a nondifferential
7 Case Control Study of Pleural Mesothelioma 7 TABLE VI. Odds Ratios in Diverse Case^Control Studies of Pleural Mesothelioma References N Exposure categories OR (95% CI) Agudo et al. , Spain 132 cases Certain 13.2 (6.4^27.3) 257 controls High probability and high intensity of exposure 27.1 (9.28^79.3) 208 cases Spirtas et al. , US 533 controls Certain cases Iwatsubo et al. , Paris, France 387 controls Certain 3.6 (2.4^5.3) Tuomi et al. , Finland 51cases Certain 17.7 (3.4^253) 51controls Likely 3 (0.9^10.6) Aguilar-Madrid Currents data, Mexico 119 cases Certain 14.3 (8^26) 353 controls Likely 3.7 (1.3^10.4) OR, odds ratio; 95% CI, 95% confidence interval. misclassification bias always dilutes the strength of the association may not hold in certain situations involving more than two exposure categories [Szklo and Nieto, 1999]. We were only able to get a hold of one hygienist, as only approximately eight certified hygienists exist in Mexico. Only one of them collaborated with us in this research project, which obviously constitutes a limitation in this study. However, the absence of an increase in risk in the likely and possible categories shows it was difficult to assign with accuracy the exposure in these intermediate categories, thus this increases the likelihood of misclassification. Nonetheless, one advantage of this classification is that it recovers and takes into account work history information of companies, workplace, and years of exposure. Also, because the employment history depends on the precision of the information provided by the worker it is considered that the validity is acceptable, because the study comprised incident cases of MPM. This permitted us to apply the questionnaire at the time of the worker s first request for medical care due to suspicion of tumor; thus, worker cases were unaware of the association between asbestos exposure and presence of mesothelioma. This allowed controlling a probable bias in over-reporting of exposure in the cases; we observed a very low schooling level in workers with MPM. This unfortunately means that their knowledge regarding the health risk for asbestos exposure is very limited; it is precisely under this premise that dangerous industries such as asbestos have been installed in Mexico. Retrospective evaluation of exposure is one of the principal problems in case control studies. Some authors have constructed exposure matrixes by workplaces [Kauppinen et al., 1998]. In these, information on the exposure levels of certain chemical substances or fibers is known, and exposure frequency and intensity can be described. In addition, Teschke et al.  mention that one of the best strategies for estimating occupational exposure lies in adding environmental measurement data. One limitation of this study is the likely underestimation of risk, due to the fact that in Mexico environmental asbestos monitoring remains unreliable, unavailable, and unpublished. Thus, we utilized information from studies published in international journals that clearly identify industries with asbestos exposure risks. Reliance on monitoring for air-borne exposure to asbestos is fraught with hazard as it is often not representative of true working conditions. But this is particularly true for malignant mesothelioma, where very low levels can result in disease. The high AR among exposed workers in this study (83.2%) indicates that this percentage of pleural mesothelioma can be attributed to occupational exposure to asbestos probably chrysotile, the variant most imported to Mexico, from Canada [Aguilar-Madrid et al., 2003]. Spirtas et al.  reported similar results in a case control study in 208 cases and 533 controls on MPM-associated to deaths from 1975 to 1980 in New York of State Health Department Cancer Registry, but also from the Los Angeles County Cancer Surveillance Program and 39 large Veterans Administration Hospitals; they obtained an AR among males due to asbestos exposure of 88% (95% CI 76 95). Also, Gennaro et al.  in a study of mortality among oil-refinery maintenance workers in Italy and Canada, revealed that % of deaths due to mesothelioma and 42 49% of lung cancers were attributable to exposure to asbestos. Our results show a clear relationship between industrial use of all types of asbestos and MPM, and in Mexico the major type of asbestos is chrysotile imported from Canada [Aguilar-Madrid et al., 2003], confirming that asbestos is a carcinogenic agent that has been recognized as such by IARC since As an addition to the case control study, we did a follow-up of the survival of the 119 cases of MPM examined and confirmed by immunohistopathology; 34.7% (24) of these individuals had died by March 2006; of these, only in 29% (7) of cases was malignant pleural mesothelioma the cause of death annotated on the decease certificate. This generates an underreporting in the official mortality data by
8 8 Aguilar-Madrid et al. mesothelioma in Mexico by approximately 71%. From this point of view, the trend shown in Figure 1 could be more pronounced: instead of 170 cases officially reported in the country (there should be 500 cases reported annually), only four cases are being recorded as occupational illness for social security [SUI-ST-5, ]. Also, in this study the cost of medical attention for each mesothelioma case during the first year or treatment was estimated at $90,625 pesos (8,238 dollars), with a minimum value of $5,531 pesos (503 dollars and maximum 368,236 pesos (3,3476 dollars). This means that for every 500 mesothelioma cases estimated by us in 2005, the mean yearly cost for medical care in the health sector, at 2005 costs, was $45,312,500 pesos (4,119,318 dollars). Thus cost is fully covered by the health system, not by the companies that created the risk, because these diseases are not recognized as work related illness. The social and economic impact of these diseases and asbestos-related deaths should be absorbed by the industries that have generated the damage and not by the health institutions, as it occurs at present. According to Hure ,... the utilization of asbestos can punish the economy of countries during more than 30 years, leaving to future generations the responsibility to indemnify the victims and the financial burden of medical care for the victims. LaDou  reported that migration of asbestos industry to developing countries increasingly bear the cost of its adverse effects, including the cost that should be borne by the asbestos industry. The increase in the number of cases of MPM is generating disease and death among Mexican workers. The transfer of this dangerous industry to Mexico with the consent of the health and labor authorities (Fig. 1), has also been encouraged by international organizations [COP3, 2006]. In this issue, Summers Lawrence  proposed that the World Bank must support the migration of dirty and toxic-waste industries to developing countries due to the logical economic reasons concerned with certain comparative advantages of these countries, including low wages; large spaces where there is still much room for contamination and the low incidence of cancer in the poor countries [Galeano, 1998]. However, reality shows us that Canada has faithfully applied the recommendations of Summers and comprises a deplorable example of the manner in which dangerous industries are being deliberately exported to Mexico and less industrialized countries. According to records from 1994 to 2003, exports of the mineral asbestos from Canada to Mexico represented $114,713,210 million USD in , ranking in 5th place with 7.8% of the total world exports of Canada. Other countries purchasing from Canada included Japan (25%), Thailand (21.2%), India (18.6%), Indonesia (8%), Korea (7.7%), the U.S. (3.5%), and Algeria (3.4%). By continuing this Mexican policy of importing this risk, cases of pleural mesothelioma will continue to increase nationwide [Trade Data Asbestos Canada 2004] (Fig. 1). The ILO  has calculated that worldwide, premature death occurs in 100, ,000 persons as a result of asbestos-associated cancers. Additionally, the exact number of persons who have been exposed to the fiber is unknown. However, a WHO estimation notes that even if exposure is FIGURE 1. Malignantpleuralmesothelioma-associatedmortalitybygender.Mexico,1979^2005.
9 Case Control Study of Pleural Mesothelioma 9 eliminated soon, there will be 5 10 million additional deaths caused by asbestos [WHO, 2006]. On May 5, 2006 the WHO cited the following: (1) all types of asbestos cause asbestosis, mesothelioma, and cancer of the lung; (2) there is no safe level of exposure to asbestos; (3) there are safe substitutes, and (4) exposure of workers and other users of asbestos-containing products is extremely difficult to control. In June 2006 at its 95th Reunion, the ILO adopted a resolution stating the following: (a) ban and suspension of all forms of asbestos and of materials that contain asbestos constitute the most efficient means of protecting workers from asbestos exposure and for preventing future asbestos-related diseases and deaths, and (b) the Asbestos Agreement of 1986, number 16, should not be put forth to justify or support the continuation of the use of asbestos, and (c) requests that the Administrative Council promote the elimination of use of all forms of asbestos and of materials containing asbestos in all of the Member States. Despite these declarations, the Mexican State has not banned asbestos use and the asbestos-exporting countries headed by Canada (followed by Russia and China) blocked the efforts of the United Nations (UN) to include chrysotile asbestos in the list of substances. This is having a very clear impact on the life of the Mexican population [COP, Communication of Progress, 2006]. Regrettably, at this meeting Mexico declared that...we support this decision, although it also declared that...we support the noninclusion of chrysotile, because for Mexico it could be difficult to carry out this, despite the Mexican Health Ministry s possessing knowledge of the tendency of the increase (23 170) in cases of malignant pleural mesothelioma (Fig. 1). This increase is similar to that reported in European countries, the U.S., and China [Karjalainen et al., 1997; Albin et al., 1999; Goodman et al., 1999; Banaei et al., 2000; Pinheiro et al., 2004; Hodgson et al., 2005]. According to Nicholson et al. , it has been estimated that for every pleural mesothelioma-associated death there are 2.3 (95% CI, 2 2.7) asbestos exposure-related deaths due to lung cancer. Application of ban asbestos in Mexico as a precautionary principle [Gee and Greenberg, 2002] of the Declaration of Rio on the Environment and Development should not only be a call to reason for the health and work authorities. In addition, it should be a call for them to comply with their obligation and commitment to safeguard the population, and their liability to guarantee the constitutional right to health and life of the Mexican population. Also, there should be a measure to halt the impunity with which the national and transnational asbestos companies operate in Mexico. CONCLUSIONS The present article is the first developed in Mexico of cases and controls involving workers in whom an estimate of exposure in categories was utilized for demonstrating that the relationship between asbestos exposure and MPM is similar to that reported by studies internationals. Based on our findings, we propose that the Mexican Government must ban the use and commercialization of all forms of asbestos so as to prevent the epidemic clearly shown using national mortality data and as an urgent measure to protect the life of future generations. Moreover, an epidemiologic surveillance program of these workers, as well as of the communities near this type of industry should be developed. Thirdly, financial expenses of medical expenses and pensions should be imposed upon asbestos manufacturers and importers in Mexico. We also show that the low educational level of the workers promotes to put them in this kind of risk because their scarce knowledge about this issue. Thus the Government should implement a national information campaign for the population on preventing and controlling exposure linked to the presence of asbestos in buildings, industrial equipment, sheet constructions, homes, drinking water, automobiles, and other products, taking into account that at present there is the technical possibility of substituting asbestos for the prevention for the mesothelioma epidemic in Mexico, which will continue to increase at least during the next 50 years if its use is not banned at once. ACKNOWLEDGMENTS We are grateful to the active workers and retirees who participated in this study for their valuable cooperation, especially those who died prematurely without knowing the reason why, without punishment of the guilty, to those who died inexorably and who even so offered us their information, and to their forsaken families, to the directors, service heads, and medical Oncologists, Pneumologists, Pathologists, and nurses at the participating hospitals, especially to social workers Amparo Gómez M and Irais I Pastelín-Ramírez for their great dedication in administering the surveys, and to Dr. Víctor Hugo Borja-Aburto, Dr. Benedetto Terracini and Dr. Luis Haro for their support and comments. REFERENCES Agudo A, González CA, Bleda MJ, Ramírez J, Hernández S, López F, Calleja A, Panades R, Turuguet D, Escolar A, Beltrán M, González- Moya JE Occupation and risk of malignant pleural mesothelioma: case-control study in Spain. 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